期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 104, 期 8, 页码 2733-2737出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.0611311104
关键词
apoptosis; cell cycle; p53-dependent; ubiquitin ligase
资金
- NCI NIH HHS [R01 CA098210, CA 23767, CA 118085, R01 CA118085, P01 CA023767, CA 098210, R56 CA098210] Funding Source: Medline
- NIAMS NIH HHS [K01 AR048582, AR 148582-03] Funding Source: Medline
The mammalian epidermis is maintained by proliferation and differentiation of epidermal progenitor cells in a stereotyped developmental program. Here we report that tissue-specific deletion of the UV-damaged DNA-binding protein 1 [DDB1) in mouse epidermis led to dramatic accumulation of c-Jun and p21Cip1, arrest of cell cycle at G(2)/M, selective apoptosis of proliferating cells, and as a result, a nearly complete loss of the epidermis and hair follicles. Deletion of the p53 tumor suppressor gene partially rescued the epithelial progenitor cells from death and allowed for the accumulation of aneuploid cells in the epidermis. Our results suggest that DDB1 plays an important role in development by controlling levels of cell cycle regulators and thereby maintaining genomic stability.
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